The ER-embedded UBE2J1/RNF26 ubiquitylation complex exerts spatiotemporal control over the endolysosomal pathway
The ER-embedded UBE2J1/RNF26 ubiquitylation complex exerts spatiotemporal control over the endolysosomal pathway
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DOI：
10.1016/j.celrep.2020.108659
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发表时间：
2021-01-19
期刊：
影响因子：
8.8
通讯作者：
Berlin, Ilana
中科院分区：
文献类型：
--
作者：
Cremer, Tom;Jongsma, Marlieke L. M.;Berlin, Ilana
内溶酶体系统履行多种细胞功能，其中许多功能通过与其他细胞器的相互作用进行调节。特别是，内质网对内体和溶酶体的组织和运动产生时空限制。我们最近将内质网跨膜 E3 泛素连接酶 RNF26 描述为内溶酶体核周定位和运输动力学的调节剂。在这里，我们报道泛素结合酶 UBE2J1 也锚定在 ER 膜上，在这种情况下与 RNF26 合作，并且所得 E2/E3 对的细胞活性位于核周 ER 亚结构域中，并受到跨膜相互作用的支持。通过对赖氨酸 435 上的 SQSTM1/p62 进行修饰，内质网嵌入的 UBE2J1/RNF26 泛素化复合物招募内体接头，将其同源囊泡固定在细胞的核周区域。由此产生的时空区室化促进激活的 EGFR 运输至溶酶体，并促进 EGF 诱导的 AKT 信号传导的终止。
The endolysosomal system fulfills a wide variety of cellular functions, many of which are modulated through interactions with other organelles. In particular, the ER exerts spatiotemporal constraints on the organization and motility of endosomes and lysosomes. We have recently described the ER transmembrane E3 ubiquitin ligase RNF26 as a regulator of endolysosomal perinuclear positioning and transport dynamics. Here, we report that the ubiquitin conjugating enzyme UBE2J1, also anchored in the ER membrane, partners with RNF26 in this context, and that the cellular activity of the resulting E2/E3 pair is localized in a perinuclear ER subdomain and supported by transmembrane interactions. Through modification of SQSTM1/p62 on lysine 435, the ER-embedded UBE2J1/RNF26 ubiquitylation complex recruits endosomal adaptors to immobilize their cognate vesicles in the perinuclear region of the cell. The resulting spatiotemporal compartmentalization promotes the trafficking of activated EGFR to lysosomes and facilitates the termination of EGF-induced AKT signaling.